Summary: Researchers report Per1, a gene that governs circadian rhythm, acts differently in women, and may protect them from heart disease.
Source: American Physiological Society.
Research suggests that a gene that governs the body’s biological (circadian) clock acts differently in males versus females and may protect females from heart disease. The study is the first to analyze circadian blood pressure rhythms in female mice. The research, published ahead of print in the American Journal of Physiology–Regulatory, Integrative and Comparative Physiology, was chosen as an APSselect article for January.
The body’s circadian clock–the biological clock that organizes bodily activities over a 24-hour period– contributes to normal variations in blood pressure and heart function over the course of the day. In most healthy humans, blood pressure dips at night. People who do not experience this temporary drop, called “non-dippers,” are more likely to develop heart disease. The circadian clock is made up of four main proteins (encoded by “clock genes”) that regulate close to half of all genes in the body, including those important for blood pressure regulation.
Previous research has shown that male mice that are missing one of the four clock genes (PER1) become non-dippers and have a higher risk for heart and kidney disease. A research team studied the circadian response and blood pressure of female mice that lack PER1 and compared them with a healthy female control group. On both low- and high-salt diets, both groups “retained an apparent circadian rhythm” of blood pressure, the researchers explained. Unlike the male mice in previous research, the females without PER1 showed normal dips in blood pressure overnight.
These results suggest that the lack of PER1 acts differently in males and females. The findings are consistent with research showing that premenopausal women are less likely to be non-dippers than men of the same age. “This study represents an important step in understanding sex differences in the regulation of cardiovascular function by the circadian clock,” the researchers wrote.
Source: American Physiological Society
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Original Research: Open access research for “Female C57BL/6J mice lacking the circadian clock protein PER1 are protected from nondipping hypertension” by Lauren G. Douma, Kristen Solocinski, Meaghan R. Holzworth, G. Ryan Crislip, Sarah H. Masten, Amber H. Miller, Kit-Yan Cheng, I. Jeanette Lynch, Brian D. Cain, Charles S. Wingo, and Michelle L. Gumz in American Journal of Physiology – Regulatory, Int. & Comparative Physiology. Published January 9 2019.
Female C57BL/6J mice lacking the circadian clock protein PER1 are protected from nondipping hypertension
The circadian clock is integral to the maintenance of daily rhythms of many physiological outputs, including blood pressure. Our laboratory has previously demonstrated the importance of the clock protein period 1 (PER1) in blood pressure regulation in male mice. Briefly, a high-salt diet (HS; 4% NaCl) plus injection with the long-acting mineralocorticoid deoxycorticosterone pivalate (DOCP) resulted in nondipping hypertension [<10% difference between night and day blood pressure (BP) in Per1-knockout (KO) mice but not in wild-type (WT) mice]. To date, there have been no studies that have examined the effect of a core circadian gene KO on BP rhythms in female mice. The goal of the present study was to determine whether female Per1-KO mice develop nondipping hypertension in response to HS/DOCP treatment. For the first time, we demonstrate that loss of the circadian clock protein PER1 in female mice does not significantly change mean arterial pressure (MAP) or the BP rhythm relative to female C57BL/6 WT control mice. Both WT and Per1-KO female mice experienced a significant increase in MAP in response to HS/DOCP. Importantly, however, both genotypes maintained a >10% dip in BP on HS/DOCP. This effect is distinct from the nondipping hypertension seen in male Per1-KO mice, demonstrating that the female sex appears to be protective against PER1-mediated nondipping hypertension in response to HS/DOCP. Together, these data suggest that PER1 acts in a sex-dependent manner in the regulation of cardiovascular rhythms.